University of California Irvine School of Medicine, Orange, CA.
Dana-Farber Cancer Institute, Boston, MA.
JCO Precis Oncol. 2024 Oct;8:e2400334. doi: 10.1200/PO.24.00334. Epub 2024 Oct 24.
Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene on chromosome 15q14. Co-occurring alternations have not been fully characterized.
We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris).
While NC is driven by fusion oncoproteins, co-occurring DNA mutations in epigenetic or cell cycle pathways were observed in 26% of cases. There was no significant difference between the fusion partner of and co-occurring gene mutations. RNA sequencing analysis showed increased pathway activity in NC compared with head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC), which is consistent with the known pathophysiology of NC. Characterization of the NC tumor microenvironment using RNA sequencing revealed significantly lower immune cell infiltration compared with HNSCC and LUSC. NC was 10× higher in patients with HNSCC and LUSC younger than 50 years than in those older than 70 years.
To our knowledge, this is the first series of NC profiled broadly at the DNA and RNA level. We observed fewer intratumoral immune cells by RNA sequencing, which may be associated with anecdotal data of lack of immunotherapy benefit in NC. High pathway activity in NC supports ongoing trials targeting suppression. The incidence of NC among patients younger than 50 years with LUSC/HNSCC supports testing for NC in these patients. The prognosis of NCs remains dismal, and future studies should focus on improving the response to immunotherapy and targeting MYC.
睾丸癌中的核蛋白（NC）是一种被低估和侵袭性的鳞状/低分化癌，其特征是染色体 15q14 上的基因发生重排。同时发生的改变尚未得到充分描述。
我们分析了 54 例接受基于 DNA 和 RNA 的 NGS 测序（Caris）的 NC 病例的基因组和免疫景观。
虽然 NC 是由 融合癌蛋白驱动的，但在 26%的病例中观察到表观遗传或细胞周期途径中的共同发生的 DNA 突变。和共同发生的基因突变之间没有显著差异。与头颈部鳞状细胞癌（HNSCC）和肺鳞状细胞癌（LUSC）相比，RNA 测序分析显示 NC 中 通路活性增加，这与 NC 的已知病理生理学一致。使用 RNA 测序对 NC 肿瘤微环境进行表征显示，与 HNSCC 和 LUSC 相比，免疫细胞浸润明显较低。在年龄小于 50 岁的 HNSCC 和 LUSC 患者中，NC 的发生率是年龄大于 70 岁患者的 10 倍。
据我们所知，这是首次在 DNA 和 RNA 水平上对 NC 进行广泛分析。我们通过 RNA 测序观察到较少的肿瘤内免疫细胞，这可能与 NC 中免疫治疗获益的轶事数据有关。NC 中 通路的高活性支持针对 抑制的正在进行的试验。年龄小于 50 岁的 LUSC/HNSCC 患者中 NC 的发生率支持对这些患者进行 NC 检测。NC 的预后仍然很差，未来的研究应集中在提高免疫治疗的反应和靶向 MYC 上。
